FAST DISSOLVING DOSAGE FORMS CONTAINING MAGNESIUM ALUMINUM SILICATE AND MULTIPLE ACTIVE INGREDIENTS

Abstract: An adsorbate composition comprising magnesium aluminum silicate and two or more pharmaceutically acceptable actives in a fast dissolving dosage form.

Description: FAST DISSOLVING DOSAGE FORMS CONTAINING MAGNESIUM ALUMINUM SILICATE AND MULTIPLE ACTIVE INGREDIENTS TECHNICAL FIELD The present invention relates to a good tasting, fast dissolving adsorbate composition consisting of magnesium aluminum silicate with two or more pharma¬ ceutically acceptable active ingredients. BACKGROUND OF THE INVENTION Adsorbates have been used for many years, masking the untoward taste of many compounds. The use of magnesium aluminum silicate in this capacity is dis¬ closed in, for example, U.S. Patent 4.711.774. Decembe-r 8, 1987; 4.716.033- De¬ cember 29, 1987; 4.758.424. July 19,1988; 4.758.425- July 19,1988; 4.761.274. Au¬ gust 2,1988 to Denic , Jr. et al., U.S. Patent 4.753.800- June 28, 1988 to Mozda and U.S. Patent 3.140.978. July 14, 1964 to Zentner. While the prior art discloses magnesium aluminum silicate as useful in mask¬ ing the taste of pharmacologically active compounds, there is still a need for fast dissolving, taste-masking formulations of this kind incorporating multiple pharma- cologjc actives. The prior art disclosures of immediate release dosage forms contain- ing magnesium aluminum silicate as the taste masking agent generally focus on masking the taste of a single pharmaceutically active ingredient. This may be attrib¬ uted to the assumption that any increase in the amount of the bitter tasting compo¬ nents) used (e.g. higher doses of the initial compound or the admixing of an addi¬ tional compound(s)) would require a corresponding increase in the amount of mag- nesium aluminum silicate used. The causal link between this assumption and the fo¬ cus of the prior art becomes evident as one appreciates the problems that arise with increasing amounts of magnesium aluminum silicate. These problems include de¬ creased disintegration time, decreased release of the pharmaceutically active ingredi¬ ent and decreased palatability (i.e. experiencing an undesirable clay taste). The pre- sent inventors, however, have discovered that despite the presence of multiple, pharmaceutically active compounds, fast dissolving dosage forms which incorporate a single taste masking agent, magnesium aluminum silicate, still retain their taste masking ability even at levels low enough to avoid the above-mentioned problems. It is therefore an object of the present invention to provide a good-tasting adsorbate composition that contains two or more phaπnacologic actives. It is a further object of the present invention to provide a good-tasting, fast dissolving composition incorporating said pharmaceutical actives. Still a further object is to provide a method of making a good tasting, quick dissolving medicament containing multiple pharmaceutical actives. These objectives and additional objectives will become readily apparent from the detailed description which follows. SUMMARY OF THE INVENTION The present invention relates to a pharmaceutical composition comprising: (a) a clay component consisting of magnesium aluminum silicate; (b) a safe and effective amount of two or more pharmaceutically acceptable active ingredients selected from the group consisting of an antitussive; an aπtinauseant a nutritional supplement; a laxative; an appetite suppressant; an analgesic; an antiasthmatic; an antihistamine; a decongestaπt; an expectorant; an antacid; an antidiarrheal, a H2-Receptor antagonist and mixtures thereof, and (c) a pharmaceutically acceptable carrier wherein said pharmaceutically acceptable carrier can be rapidly disintegrated in aqueous solution. The present invention further relates to methods of treating symptoms such as those associated with the common cold, respiratory disorders, cough, cold, cold-like and or fiu symptoms associated with the common cold, gastrointestinal disorders and allergies; comprising the administration of a safe and effective amount of the com¬ positions of the present invention. All percentages and ratios herein are by weight unless otherwise specified. Additionally, all measurements are made at 25°C unless otherwise specified. By "safe and effective amount," as used herein, is an amount that is effective to mitigate and/or treat the symptoms for which the active ingredient is indicated in a human without undue adverse side effects commensurate with a reasonable risk/benefit ratio. .ψ An Γ> DESCRIPTION OF THE INVENTION The compositions of the present invention contain essential components as well as various nonessential components as indicated below. ESSENTIAL COMPONENTS Magnesium Aluminum Silicate The first essential component of the present invention is a safe and effective amount of magnesium aluminum silicate of the formula Al2MgOgSi2.. Magnesium aluminum silicate occurs naturally in such smectite minerals as colerainite, saponhe, sapphirine, sheridanite zebedassite and has been used extensively in a variety of cos- metic and pharmaceutical formulations. The refined magnesium aluminum silicates used in the present example, Veegum® HS, is available from and manufactured by R.T. Vanderbilt Company, Inc., Norwalk, CT. A Typical chemical analysis of Veegum® HS, is as follows: Silicon dioxide 63.0 Magnesium oxide 10.5 Aluminum oxide 10.5 Ferric oxide 0.9 Calcium oxide 2.3 Sodium oxide 2.4 Potassium oxide 1.2 Ignition loss 7.5 having a combined density of 2.6mg/m^. The compositions of this invention typically comprise from about 0.01% to about 50%, preferably from about 0.1% to about 25%, more preferably from about 1.0% to about 10% and most preferably from about 1.0% to about 5%, by weight of a magnesium aluminum silicate. Magnesium aluminum silicates are described more fully in, for example, U.S. Patent 4.761.274. August 2, 1988, to Denick, Jr. et al.; U.S. Patent 4 753 800 June 28, 1988, to Mozda, and U.S. Patent 3.140.978. July 14, 1964 to Zentoer, all of which are herein incorporated by reference. Pharmaceutically acceptable actives The two or more pharmaceutically acceptable actives useful in the present invention may be selected from among the various groups of chemical compounds or materials suitable for oral administration and having a pharmacological action. These pharmaceutically acceptable active compounds or materials should be compatible with the other essential ingredients and compatible in combination with other in¬ cluded active materials or compounds. The pharmaceutically acceptable active com¬ pounds or materials are present at a level from about 0.01% to about 75%, preferably from about 0.1% to about 50%, more preferably from about 1.0% to about 25% and most preferably from about 1.0% to about 10%. Useful pharmaceutically acceptable active materials or compounds may include, but are not limited to: bronchodilators, anorexiants, antihistamines, nutritional supplements (such as vitamins, minerals, fatty acids, amino acids, and the like), laxatives, analgesics, antacids, H2~receptor antago- nists, antidiarrheals, decongestants, antitussives, antinauseants, antimicrobials, anti- fungals, antivirals, expectorants, anti-inflammatory agents, antipyretics, their pharma¬ ceutically acceptable salts and mixtures thereof. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases including inorganic bases and organic bases. Salts derived from inorganic bases include sodium, potassium, lithium, am¬ monia, calcium, magnesium, ferrous, zinc, manganous, aluminum, ferric, manganic salts and the like. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, tertiary and quaternary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as triethyiamine, tripropylamine, 2-dimethyiaminoethanol, 2- diethylaminoethanol, lysine, arginine, histidine, caffeine, procaine, N-ethylpiperidine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglycaniine, theo- bromine, purines, piperazine, piperidine, polyamine resins and the like. Examples of decongestants useful in the compositions of the present inven¬ tion include pseudoephedrine, phenylpropanolamine, phenylephrine and ephedrine, their pharmaceutically acceptable salts, and mixtures thereof. Examples of antitussives useful in the compositions of the present invention include dextromethorphan, chlopedianol, carbetapentane, caramiphen, noscapine, diphenhydramine, codeine, hydrocodone, hydromorphone, their pharmaceutically ac¬ ceptable salts, and mixtures thereof. Examples of expectorants (also known as mucolytic agents) useful in the pre- sent invention include; glycαyi guaiacolate, terpin hydrate, ammonium chloride, N- acetylcysteine, and a broxol, their pharmaceutically acceptable salts, and mixtures thereof Examples of analgesics useful in the present invention include; morphine, co¬ deine, meperidine, pentazoάne, propoxyphene, acetaminophen, allopurinol, acetyl- salicylic acid, choline salicylate, ketoprofen, magnesium silicate, fenoprofen, ibupro- fen, indomethacin, naproxen, and many others and their pharmaceutically acceptable salts and mixtures thereof. Examples of antihistamines useful in the present invention include; brom- pheniramine, chlorpheniramine, clemastine, dexchlorpheniramine, diphenhydramine, doxylamine, promethazine, terfenadine, triprolidine and many others and their phar¬ maceutically acceptable salts and mixtures thereof. Analgesics, decongestants, antihistamines, expectorants and antitussives, as well as their acceptable dosage ranges are described in U.S. Patent 4.783.465 to Sun¬ shine et al., issued November 8, 1988, and U.S. Patent 4.619.934 to Sunshine et al., issued October 28, 1986, which are incorporated by reference herein. Examples of gastrointestinal agents suitable for use in the present invention include anticholinergics, including atropine, clidinium and dicyclominc; antacids, in- eluding aluminum hydroxide, bismuth subsalicylate, simethicone, calcium carbonate and magaldrate; H2-receptor antagonists including: cimetidine, famotidine, nizatidine and ranitidine; laxatives, including: phenolphthalein and casanthrol; and antidiar- rheals including: diphenoxylate and loperamide. Further examples of suitable analgesics, decongestants, antitussives, expecto¬ rants and antihistamines as well as bronchodilators, anorexiants, laxatives, antiemet- ics, antimicrobials, antibacterial*, antϋungals, anti-inflammatory agents, antivirala, antipyretics, nutritional supplements, anticholinexgjcs, antacids, H2-receptor antago¬ nists, antidia rheals and other misceflaneous gastrointestinal compounds and their ac- ceptable dosage ranges are described in Remington's Pharmaceutical Sciences, pp. 734-789, 791-799, 861-868, 907-945, 875-888, 1002-1034, 1098-1121, 1124-1131, 1173-1224, 1232-1241, (Alfonso R.Gennaro, editor) (18th ed. 1990), herein incor¬ porated by reference. NONESSENΠAL COMPONENTS Persons skilled in the art will quickly realize many other ingredients will be suitable for inclusion into the present invention. Nonessential components include, but are not limited to: coloring agents; flavoring agents, including: vanilla, cherry, grape, orange, peppermint, spearmint, anise, blueberry raspberry, banana, chocolate, caramel, strawberry, lemon, menthol and Prosweet™ MM50 (a combination of natu- ral and artificial flavors and propylene giycol, available from Virginia Dare Extract Co., Inc., Brooklyn, NY); sweeteners, including saccharin, dextrose, levulose, su¬ crose, cyclamate, mannitol and aspartate, along with many others; suspending agents, including xanthum gum, acacia gum, carboxymethylcellulose, starch and methylcellu- lose; preservatives; releasing agents, including polysorbate 80, sodium lauryl sulfate, vegetable oils and magnesium stearate; and water. Another preferred nonessential component of the present invention is a cool¬ ing agent or a combination of cooling agents. Suitable cooling agents are those des¬ cribed in U.S. Patent 4.136.163. January 23, 1979, to Watson et al., U.S. Patent 4.230.668. October 28, 1980, to Rowsell et al. and U.S. Patent 4.032.661, to Rowsell et al., all of which are herein incorporated by reference. A particulariy pre¬ ferred cooling agent is N-ethji-p-menthane-3-carboxamide (WS-3 supplied by Ster¬ ling Organics), taught by the above incorporated U.S. Patent 4.136.163. Another particularly preferred cooling agent is 3-1-menthoxypropane 1,2-diol (TK-10 sup¬ plied by Takasago Perfumery Co., Ltd., Tokyo, Japan). This material is described in detail in U.S. Patent 4.459.425. July 10, 1984 to Amano et al. and incorporated herein by reference. METHOD OF MANUFACTURE Good tasting pharmaceutical adsorbate compositions of the present invention are prepared using art-recognized principles and methodologies in mixing the ingre¬ dients together and in choosing the type of mixing equipment to be used. However, because of the potential for adverse interactions between the magnesium aluminum silicate and various multiply charged cationic drugs (e.g. chlorpheniramine) - result¬ ing in poor drug dissolution, it is important that certain measures be followed to insure effective drug dissolution. Such a situation is described in McGinty, J.W. and Lach, J.L., In Vitro Adsorption of Various Pharmaceuticals to Moπtmorillont Jour. of Pharm. Sd., 65, 896-902 (1976) and is herein incorporated by reference. By "multiply charged cationic drugs" as used herein, means compounds containing more than one positively charged substhuent The crucial steps involve maintaining the pH in a range equal to or above that of the pKa of the multiply charged cationic drug(s) and, additionally, reserving the addition of said multiply charged cationic dmg(s) until after the addition of at least one other cationic compound. After the ingredients of the present invention are combined, the mixture may then be compounded with effervescent or other water-dispersible substances and dried into dosage forms that rapidly disintegrate upon coming into contact with an aqueous liquid. Suitable effervescent technology is described in chapter 6 of Phar- maceutical Dosape Forms: Tablets. Vol. I, 2 nd ed., A Lieberman ed., 1989, Marcel Dekker, Inc. herein incorporated by reference. The above mentioned compounding and drying process may be accomplished by using any of a multitude of solid dosage forming techniques and equipment. Methods of solid dosage formulation are well known in the art and any appropriate method may be utilized. Further information regarding solid dosage formulation can be found in Remington's Pharmaceutical Sri- ences. pp. 1633-1664, (Alfonso R. Gennaro, editor) (18th ed. 1990). Alternatively, the resultant fast dissolving dosage form may be achieved by freeze drying. Freeze-drying or ryophilization facilitates disintegration of the com¬ position by forming the dried composition into an open matrix network. In most cases, this results in rapid permeation by the aqueous media, promoting timely delivery of the product's active ingredients. Suitable methods of freeze drying are well known in the art and commonly employed. Any suitable conventional method of freeze-drying or vacuum-drying may be utilized. A preferable method of freezing and drying is to fast freeze the composition and then dry the composition to a final moisture content of about 2% to about 5%. Suitable methods of freeze-drying and production are taught by U.S. Patent 4.642.903. February 17, 1987, to Davies, U.S. Patent 4.946.684. August 7, 1990, to Blank et al., U.S. Patents 4.305.502 and 4.371.516 . issued December 15, 1981 and February 1, 1983 respectively, to Gregory et al., and U S Patent 5.188.825. February 23, 1993, to lies et al.; which are all in¬ corporated herein by reference One other form of fast dissolving technology that may be applicable to the present invention is that devdoped by Janssen Pharmaceutica Inc. and is identified by the trade name Quicksolv™. This technology is fully described in U.S. Patent 5.215.756. herein incorporated by reference. EXAMPLES The following examples further describe and demonstrate embodiments whhin the scope of the present invention. The examples are given solely for the pur¬ pose of illustration and are not to be construed as limitations of the present invention, as many variations are possible without departing from the spirit and scope of the in¬ vention. EXAMPLE I Ingredients W V% chloφheniramine maleate 0.13300 phenylpropanolamine HC1 0.83300 magnesium aluminum silicate 0.50000 xanthum gum 0.20000 potassium sorbate 0.07500 polysorbate 80 0.10000 Prosweet™ MM24 2 0.50000 sodium saccharin 0.05000 aspartame 0.30000 monoammonium gtycyπhizate^ 0.03000 sucrose 5.00000 mannitol 10.00000 3-1-menthoxypropane 1,2-diol 4 0.07000 N-ethyl-p-menthane-3-carboxamide^ 0.02000 menthol, natural 0.26600 peppermint flavor 0.18000 purified water q.s. to 100 available as Veegum® HS from RT. Vanderbilt, Norwalk, CT. 2 Available from Virginia Dare Extract Co., Inc., Brooklyn, NY. 3 Available as Magnasweet 185 supplied by McAndrews & Forbes, Camden, NJ. 4 Available as TK-10 supplied by Takasago Perfumery Co. 5 Available as WS-3 supplied by Sterling Organics. In an appropriately sized container, with Lightnin™ mixer (model #TS2010 (or a high shear homogenizer set at 30 to 50 RPM)) mixing at approximately 250 to 1000 RPM, add the following agents allowing each to dissolve before adding the next: water, phenylpropanolamine HC1, Veegum® HS. Heat, using a hot plate, keeping solution at 77°C, and mix vigorously (250 to 1000 RPM) for 30 minutes. Turn heat off and allow mixture to cool to room temperature (25°C) while mixing for a minimum of an additional 15 minutes. Add monoammonium glycyrrhizate, Prosweet™ MM24, potassium sorbate, aspartame, sodium saccharin, WS-3 and peppermint. Separately, dry blend mannitol, sucrose, and xanthum gum and add slowly to the original mixture. Separately dissolve chlorpheniramine maleate with a suffident amount of water and add to the original mixture. Adjust the volume to 1.5000 liters and mix for 15 minutes. Separate from the above mixture, in an appropriate con¬ tainer, add polysorbate 80, TK-10, and menthol. Add this mixture to the original mixture while continuing mixing. As the mixing continues, place 1.5 ml of solution into molds and freeze-dry or vacuum-dry the composition. This process, in turn, provides a pharmaceutical adsorbate composition having improved taste. Admini¬ stration of two tablets to an adult human is the normal and customary dosage for use in treating the symptoms of a respiratory illness or allergy. EXAMPLE π Ingredients W/V% chlorpheniramine maleate 0.13300 phenylpropanolamine HC1 0.83300 magnesium aluminum silicate 0.50000 xanthum gum 0.20000 potassium sorbate 0.07500 polysorbate 80 0.10000 Prosweet™ MM24 0.50000 sodium saccharin 0.05000 aspartame 0.30000 monoammonium glycyrrhizate 0.03000 sucrose 5.00000 mannitol 10.00000 3-1-menthoxypropane 1,2-diol 0.07000 N-ethyi-p-menthane-3-carboxamide 0.02000 menthol, natural 0.26600 lemon flavor 0.40000 color, FD&C Yellow #6 0.00240 purified water q.s. to 100 EXAMPLE m Ineredients W VV, chlorpheniramine maleate 0.13300 phenylpropanolamine HC1 0.83300 magnesium aluminum silicate 0.50000 xanthum gum 0.20000 potassium sorbate 0.07500 10 polysorbate 80 0.10000 Prosweet™ MM24 0.50000 sodium saccharin 0.05000 aspartame 0.30000 monoammonium glycyrrhizate 0.03000 15 sucrose 5.00000 mannhol 10.00000 3-1-menthoxypropane 1,2-diol 0.07000 N-ethyl-p-menthane-3-carboxamide 0.02000 menthol, natural 0.26600 20 raspberry flavor 0.30000 color, FD&C Yellow #6 0.00236 color, FD&C Red #33 0.00326 purified water q.s. to 100 EXAMPLE IV 25 Ingredients W V% diphenhydramine HC1 0.83300 phenylpropanolamine HC1 0.83300 magnesium aluminum silicate 0.50000 xanthum gum 0.20000 30 potassium sorbate 0.07500 polysorbate 80 0.10000 Prosweet™ MM24 0.50000 sodium saccharin 0.15000 aspartame 0.30000 35 monoammonium glycyrrhizate 0.03000 sucrose 5.00000 mannitol 10.00000 3-1-menthoxypropane 1,2-diol 0.07000 N-ethyl-p-menthane-3-carboxamide 0.02000 menthol, natural 0.26600 lemon flavor 0.20000 menthol monophosphate 0.30000 purified water q.s. to 100 EXAMPLE V Ingredients A^t triprolidine HQ 0.16700 10 phenylpropanolamine HC1 0.83300 magnesium aluminum silicate 0.50000 ascorbic add 2.00000 xanthum gum 0.20000 potassium sorbate 0.07500 15 polysorbate 80 0.10000 Prosweet™ MM24 1.00000 sodium saccharin 0.15000 aspartame 1.00000 monoammonium glycyrrhizate 1.00000 20 sucrose 5.00000 mannitol 10.00000 3-1-menthoxypropane 1,2-diol 0.07000 N-ethyl-p-menthane-3-ca-rboxamide 0.02000 menthol, natural 0.26600 25 lemon flavor 0.40000 purified water q.s. to 100 EXAMPLE VI Ingredients W/V% chlorpheniramine maleate 0.13300 30 phenylpropanolamine HC1 0.83300 magnesium aluminum silicate 2.00000 calcium carbonate 1 0.80000 xanthum gum 0.20000 potassium sorbate 0.07500 35 polysorbate 80 0.10000 Prosweet™ MM24 0.50000 sodium saccharin 0.15000 aspartame 0.30000 monoammonium glycyrrhizate 0.03000 sucrose 5.00000 mannitol 10.00000 3-1-menthoxypropane 1,2-diol 0.07000 N-ethyl-p-menthane-3-carboxamide 0.02000 menthol, natural 0.26600 peppermint flavor 0.18000 purified water q.s. to 100 1 Granulated caldum carbonate containing 93.3% caldum carbonate, 6.3% glucose and 0.4% gelatin; supplied by WUttaker, Clark & Daniels, Philadelphia, PA Examples II- VI are further examples of combinations used in treating the symptoms of a respiratory illness or allergy in a human and are manufactured in a manner substantially similar to Example I. Administration of two tablets is the nor¬ mal and customary dosage. EXAMPLE Vπ Ingredients V% magnesium aluminum silicate 8.48900 loperamide 2.44000 polysorbate 80 0.04000 sodium saccharin 0.05200 aspartame 0.05200 sucrose 14.00000 mannitol 12.25500 Novag RCN-15 1 1.60000 lemon Flavor 0.47200 vanilla Creme 0.15000 ritric add 0.45000 purified water q.s. to 100 EXAMPLE Vm Ingredients W V% magnesium aluminum silicate 4.00000 bismuth subsalicylate 21.69930 polysorbate 80 0.03500 sodium saccharin 0.04550 aspartame 1.00000 sucrose 2.00000 mannitol 4.15000 Novagel RCN-15 1 1.40000 strawberry flavor 0.54600 vanilla creme 0.54990 citric add 0.06690 Klucd EF NF 2 0.25200 Antifoam AF^ 0.21000 purified water q.s. to 100 EXAMPLE DC Ingr?diςnts W/V% magnesium aluminum silicate 4.00000 simethicone 3.50000 polysorbate 80 0.03500 sodium saccharin 0.04550 aspartame 0.04550 sorbhol 0.70000 sucrose 8.25000 mannitol 16.29800 Novagd RCN-15 1 1.40000 cheπy flavor 0.19460 vanilla creme 0.24780 dtric add 0.28320 Antifoam AF^ 0.21000 purified water q.s. to 100 1 Supplied by FMC Corporation, Philadelphia, Pennsylvania 2 Supplied by AQUALON, Hopewell, Virginia 3 Supplied by Dow Corning, Midland, Michigan Examples VΗ -DC are further examples of combinations used in treating the symptoms of gastrointestinal illnesses in humans and are manufactured in a manner substantially similar to Example I. Administration of two tablets is the normal and customary dosage.

Claims: What is Claimed is: 1. A pharmaceutical composition comprising' (a) a clay component consisting of magnesium aluminum silicate: (b) a safe and effective amount of at least two pharmaceutically ac¬ ceptable active ingredients selected from the group consisting of: an antitussive; an antinauseant; a nutritional supplement, a laxa¬ tive; an appetite suppressant; an analgesic; an antiasthmatic, an antihistamine; a decongestant; an expectorant; an antacid; an an- tidiarrheal, a H2-Receptor antagonist and mixtures thereof, preferably phenylpropanolamine and chlorpheniramine; and (c) a pharmaceutically acceptable carrier wherein said pharmaceuti¬ cally acceptable carrier can be rapidly disintegrated in aqueous solution. 2. A pharmaceutical composition according to Claim 1 wherein said carrier is a freeze-dried matrix, an effervescent system, or a liquid/liquid extract system. 3. A pharmaceutical composition according to any one of the preceding Claims wherein the composition additionally contains one or more sweetening agents, preferably selected from the group consisting of sodium saccharin, aspartame, monoammonium glycyrrhizate, sucrose, mannitol and mixtures thereof. 4. A pharmaceutical composition according to any one of the preceding Claims wherein the composition additionally contains one or more flavoring agents. 5. A pharmaceutical composition according to any one of the preceding Claims wherein the composition additionally contains one or more releasing agents. 6 . A pharmaceutical composition according to any one of the preceding Claims wherein the composition additionally contains one or more cooling agents. 7 A pharmaceutical composition according to any one of the preceding Claims additionally comprising a flavoring agent selected from the group consisting of : menthol, peppermint, spearmint, raspberry, cherry, orange, vanilla, anise, blueberry, banana, chocolate, caramel, strawberry, lemon, grape and mixtures thereof. 8. A pharmaceutical composition according to any one of the preceding Claims additionally comprising a releasing agent selected from the group consisting of: polysorbate 80, sodium lauryl sulfate, magnesium stearate and mixtures thereof. 9. A pharmaceutical composition according to any one of the preceding Claims additionally comprising a cooling agent selected from the group consisting of 3-1-methoxypropane 1,2-diol, N-ethyl-p-methane-3-carboxamide and mixtures thereof. 10. A pharmaceutical composition according to any one of the preceding Claims wherein the ratio of said magnesium aluminum silicate to said phenylpropanolamine and said chlorpheniramine is 1 to 5.0 and 1 to 0.8 respectively.

Inventors: BRIDEAU MICHELLE ELIZABETH, CARELLA ANNE MARIE, BRIDEAU, MICHELLE, ELIZABETH, CARELLA, ANNE, MARIE
Applicants: PROCTER & GAMBLE, THE PROCTER & GAMBLE COMPANY
Application year: 1994
Main classification: A61K9
IPC codes: A61K9, A61K31, A61K45, A61K47